Page 52 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk

CHAPTER 3
Reference Cohort; variables
Numbers
Immuno- chip/ CORRONA: 11366/2206 RA 15489/1863 controls
NHS/EIRA: 381/1752 RA 410/1361 controls
Results
Genetic loci combined - Immunochip: OR 2.0 (CI: 2.0-2.0), AUC 0.74, sens 35%, spec 91%
Genetic loci combined - CORRONA: OR 2.0 (CI: 1.9-2.1), AUC 0.72, sens 30%, spec 92%
Addition of smoking improved the AUC to 0.80, without improving sens and spec
Genetic loci combined - NHS:
AUC 0.62 (CI: 0.58-0.67)
Genetic loci and clinical parameters: AUC 0.74 (CI: 0.70-0.78)
Genetic loci combined - EIRA:
AUC 0.58 (CI: 0.55-0.60)
Genetic loci and clinical parameters: AUC 0.69 (CI: 0.67-0.72)
Yarwood 2015(17)
Sparks 2015(13)
Immunochip Consortium Validation in CORRONA Genetic loci: 45 SNPs, imput- ed amino acids at HLA-DRB1 (11, 71 and 74) and HLA- DPB1 (position 9) HLA-B ( position 9)
Clinical parameters: gender, smoking
NHS, USA (only females) Validation in EIRA, Sweden Genetic loci: 8 HLA alleles, 31 SNPs
Clinical parameters: family history, epidemiologic fac- tors, HLA-smoking interac- tion
ACPA= anti-citrullinated protein antibodies, AUC= area under the receiver operating characteristic curve, CI= confidence interval (excluding 0,50 means statistically significant predictive value), CORRONA= Consortium of Rheumatology Researchers of North America registry, EHR= Electronic Health Records, EIRA= Epidemiologic Investigation of Rheumatoid Arthritis, HLA= human leucocyte antigen, NHS= Nurses’ Health study, RA= rheumatoid arthritis, SE= shared epitope, sens= sensitivity, SNPs= single-nucleotide polymorhisms, spec= specificity, UA= undifferentiated arthritis, UK= United Kingdom, UKRAGG= RA Genetics Group Consortium UK, USA= united states of America, WTCCC= Wellcome Trust Case Control Consortium
Environmental and behavioral factors
New risk factors for RA are being found, and systematic reviews have reevaluated established or controversial risk factors. The present situation is summarized in Table 2(5, 6).
One controversial factor was alcohol consumption, which was shown earlier to be protective, even in small quantities(6). Two reviews (18, 19) confirmed this protective effect, although the effect size was small (summary ORs of 0.78 and 0.86, respectively), and one only found the effect in individuals later developing ACPA-positive RA. A nonlinear relationship was found in the dose-response meta-analysis. Lu et al. confirmed the finding that the association between alcohol and less development of RA was stronger in seropositive women(20). Second, fish consumption (number of servings per week) was addressed in a systematic review(21). This dose-response meta-analysis showed an inverse association between fish consumption of one to three servings per week versus never consumption and the risk of RA, with a relative risk (RR) of 0.76 (CI: 0.57-1.01) (not statistically significant). Third, the meta-analysis of the consumption of coffee and tea showed that only the use of coffee was related to RA development.
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